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SULFUR COMPOUNDS AS INHIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE

The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2555 – PubChem

 

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Investigating spectrum of biological activity of 4- and 5-Chloro-2-hydroxy-N-[2-(arylamino)-1-alkyl-2-oxoethyl]benzamides

In this study, a series of twenty-two 5-chloro-2-hydroxy-N-[2-(arylamino)- 1- alkyl-2-oxoethyl]benzamides and ten 4-chloro-2-hydroxy-N-[2-(arylamino)-1- alkyl-2- oxoethyl]benzamides is described. The compounds were analyzed using RP-HPLC to determine lipophilicity. Primary in vitro screening of the synthesized compounds was performed against mycobacterial, bacterial and fungal strains. They were also evaluated for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. The compounds showed biological activity comparable with or higher than the standards isoniazid, fluconazole, penicillin G or ciprofloxacin. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds as well as their structure-activity relationships are discussed.

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Imidazolopiperazines: Lead optimization of the second-generation antimalarial agents

On the basis of the initial success of optimization of a novel series of imidazolopiperazines, a second generation of compounds involving changes in the core piperazine ring was synthesized to improve antimalarial properties. These changes were carried out to further improve the potency and metabolic stability of the compounds by leveraging the outcome of a set of in vitro metabolic identification studies. The optimized 8,8-dimethyl imidazolopiperazine analogues exhibited improved potency, in vitro metabolic stability profile and, as a result, enhanced oral exposure in vivo in mice. The optimized compounds were found to be more efficacious than the current antimalarials in a malaria mouse model. They exhibit moderate oral exposure in rat pharmacokinetic studies to achieve sufficient multiples of the oral exposure at the efficacious dose in toxicology studies.

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GUANIDINO-SUBSTITUTED QUINAZOLINONE COMPOUNDS AS MC4-R AGONISTS

A variety of small molecule, guanidine-containing molecules capable of acting as MC4-R agonists are provided. The compounds are useful in treating MC4-R mediated diseases when administered to subjects. The compounds have the structure IA, IB, and IC where the values of the variables are defined herein.

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COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS

The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.

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Chiral oxime ethers in asymmetric synthesis. 3. Asymmetric synthesis of (R)-N-protected alpha-amino acids by the addition of organometallic reagents to the ROPHy oxime of cinnamaldehyde

A new asymmetric synthesis of alpha-amino acids is described in which the key step is the diastereoselective addition of organometallic reagents to (R)-O-(1-phenylbutyl)cinnamaldoxime 5 to give hydroxylamines 6. Subsequent reductive cleavage of the N-O bond in the hydroxylamine 6 followed by N- protection gave the carbamates 7, which upon oxidation with ruthenium(III) chloride/periodate gave the N-protected amino acids 8. The method was also adapted to the synthesis of a quaternary amino acid 15 from the ketoxime ether 9.

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Stereoselective Micellar Catalysis. Part 3. Co-operative Effects of N-Decanoyl-L-histidine for the Hydrolysis of Enantiomeric Substrates

The catalytic activities of N-decanoyl-L-histidine (Ia) and its methyl ester (Ib) toward the hydrolyses of enantiomeric substrates (II) have been investigated in the presence of cetyltrimethylammonium bromide micelles.The comparison of catalytic effects (both the rate constants and stereoselectivities) of (Ia) and (Ib) strongly suggests that carboxylate ion of (Ia) intramolecularly enhances the reactivity of the imidazole group.The presence of co-operative effects is also supported by the pH-rate profile and by the thermodynamic parameters of the reaction.

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Pyridazine | C4H4N2653 – PubChem

 

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Synthesis and Biological Activity of Tetrameric Ribitol Phosphate Fragments of Staphylococcus aureus Wall Teichoic Acid

A systematically designed and synthesized ribitol phosphate (RboP) oligomer using a series of building blocks, which make up the wall teichoic acid (WTA) of S. aureus, is presented. Based on the use of a solution-phase phosphodiester synthesis, a library of ribitol phosphate tetramers, decorated with d-alanine and N-acetylglucosamine (GlcNAc), were generated. The synthesized RboP tetramers showed increased cytokine levels in mice in a subcutaneous air pouch model.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2664 – PubChem

 

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Remarkable effects of donor esters on the alpha-chymotrypsin-catalyzed couplings of inherently poor amino acid substrates

The extremely low efficiency during the alpha-chymotrypsin-catalyzed coupling of an inherently poor amino acid substrate, e.g., alanine, using the methyl ester as an acyl donor was significantly improved using esters such as the 2,2,2-trifluoroethyl or carbamoylmethyl ester. The ameliorating effect of the latter ester was especially significant.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2703 – PubChem

 

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Synthesis, pharmacological profile and 2D-QSAR studies of curcumin-amino acid conjugates as potential drug candidates

A series of curcumin bis-conjugates 3a-q, 5a-k and 6a-k were synthesized in good yields utilizing an optimized reaction condition. We explored the effect of different amino acids and protecting groups on biological activities of curcumin. The conjugates were screened for anti-inflammatory, analgesic and antimicrobial properties. Some of the conjugates showed promising biological observations with a potency comparable with the standard references. The variations in biological properties concerning different amino acids and protecting groups are interesting observations. Effects of the synthesized conjugates on splenocytes and the production of nitric oxide by lipopolysaccharide-stimulated peritoneal macrophages are correlated with the observed anti-inflammatory properties. We have also established the safety profile of the most active conjugates. Robust 2D-QSAR studies supported and validated biological data.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2721 – PubChem